The management of hemostasis (also known as blood clotting) is an important requirement for a successful surgery. The exposure of blood to foreign surfaces, which often occurs during surgery, as well as the surgery itself can induce the activation of the clotting mechanism.
The clotting mechanism can be mediated in a variety of ways. One of the more common methods of mediating coagulation is to administer heparin.
The administration of heparin, however, must be done carefully. Care is required because the response of any one patient to a particular dose of heparin is highly variable, depending upon the particular physiology of each patient. Thus, it is often quite necessary for physicians or other care givers to understand the exact blood physiology of a patient such that a proper heparin dosage may be administered.
The Medtronic HMS Plus(trademark) hemostasis management system may be used to measure many blood parameters, including activated clotting time (ACT). The Medtronic HMS Plus(trademark) system uses an ACT to measure a heparin dose response methodology. The heparin dose response curve may be seen in FIG. 1.
The heparin dose response requires a small sample of whole blood from a patient. The whole blood is introduced into particular assay channels or vials, at least one (and preferably two) of the assay vials having no heparin reagent, at least one (and preferably two) more assay vials having a heparin reagent concentration of A and at least one (and preferably two) more assay vials having a heparin reagent concentration of B, where the concentration denoted as A is different from the concentration denoted as B.
The test begins by introducing the same volume of blood into each of the channels or vials. Thereafter the blood is mixed (preferably using a plunger.) The blood clots in each of the channels or vials at differing times. The clot is measured by timing the descent rate of the plunger. Ultimately, the clotting of each of the vials or channels may graphed as shown in FIG. 1, where line 1 may be draw through the three data points created by the formation of a blood clot in each channel or vial. That is, blood without any reagents (depicted here as data point DPO), blood with heparin reagent concentration A (depicted here as data point DPA) and blood with heparin reagent concentration B (depicted here as data point DPB). As seen, the heparin dose response is a linear function when the ACT is used to initiate coagulation.
The heparin dose response line varies from patient to patient. That is, the linear heparin dose response seen in FIG. 1 has differing slopes for differing patients. Patients may have a heparin dose response line having slopes such as those seen as line 1xe2x80x2 (very low slope) or line 1xe2x80x3 (very high slope.) Generally speaking, the flatter or lower the slope of the line the more heparin resistant the patient is. Heparin resistant patients may have a variety of factors at work accounting for the heparin resistance. For example, these patients may have mechanisms which complex or bind the heparin, not allowing the heparin to inhibit blood coagulation. There may also be mechanisms present in the patient that rapidly eliminate the heparin. Finally, these patients may be heparin resistant due to their levels of the serine protease inhibitor antithrombin III (AT III). Heparin is a catalyst, that is, it helps prevent coagulation by accelerating the natural anticoagulant mechanisms present in the patient. The primary mechanism is the inhibition of thrombin, the primary protease of blood coagulation, by AT III. Without adequate amounts of AT III, heparin is ineffective in prevent blood coagulation.
AT III targets proteases of the coagulation cascade, and in particular thrombin. Heparin accelerates the rate with which AT III inhibits the proteases. Thus, without the presence of ACT III, the anticoagulant activity of heparin is severely diminished. The differences in which individuals respond to heparin may be affected by the differences in their AT III levels. Thus, a goal of the present system is to provide a method of assessing the heparin dose response while further accessing whether such heparin dose response is attributable to presence or absence of sufficient levels of AT III within the patient.
Thus there exists a need for a method and device which may reliably sense the heparin dose response of fresh whole blood as well as whether the fresh whole blood (and thus patient) has, or requires additional, AT III.
The present invention provides a method and device for testing a sample of fresh whole blood. In particular the present invention provides a method and device for testing a sample of fresh whole blood to determine whether a patient would benefit from the administration of a blood factor (such as AT III.) Patients may benefit from such an administration both prior to surgery as well as for other reasons, such as if a patient suffers from acute myocardial ischemia. The blood factor may be a factor which is involved with the coagulation cascade. In the preferred embodiment the blood factor is the serine protease inhibitor Antithrombin III (AT III). The method of the present invention determines whether a patient would benefit from the administration of a blood factor prior to surgery through the testing of a whole blood sample within at least three testing channels, a first channel, a second channel and a third channel. Preferably the at least three channels are provided within an integral cartridge. The first channel is a control channel and contains a portion of a single whole blood sample without any additives. The second channel contains a portion of the single whole blood sample along with a thrombotic/hemorrhagic agent. The third channel contains a portion of a the single whole blood sample along with the thrombotic/hemorrhagic agent and a blood factor which is involved in controlling the coagulation cascade. In the preferred embodiment the thrombotic/hemorrhagic agent which may be selected from glycosaminoglycans which have the anticoagulant sequence which binds to the blood factor which is involved in controlling the coagulation cascade. In the preferred embodiment the thrombotic/hemorrhagic agent is heparin and the blood factor which is involved in controlling the coagulation cascade is AT III. Each channel is provided with a device for assessing when a clot is formed. The time for the formation of a clot in each channel may be used to determine whether the patient would benefit from the administration of a blood factor prior to surgery. In the preferred embodiment the method may be performed within the Medtronic Hepcon HMS Plus(trademark) Hemostasis Management System. The device of the present invention may be practiced through a test cartridge used within the Medtronic Hepcon HMS Plus(trademark) Hemostasis Management System but modified to contain the appropriate reagents, identified above, in the testing cartridges.
The present invention, furthermore, is advantageous, as it performs such tests on a sample of fresh whole blood, as opposed to citrated blood. The use of fresh whole blood as opposed to citrated blood is generally preferred, since the inclusion of citrate into blood affects blood characteristics, and thus the test. In particular, citrate causes platelets to activate. Over time, moreover, citrate itself affects clotting. Both of these affects may lead to misleading test results, possible affecting patient care. In view of these deficiencies with citrated blood, past efforts have been made to compensate or mediate the affects of citrate in blood. See, for example, Baugh et al. U.S. Pat. No. 4,871,677 xe2x80x9cMethod Of Collecting And Analyzing A Sample Of Blood When Monitoring Heparin Therapy.xe2x80x9d Such past efforts, while of some benefit, have not met with ideal results.